A Prospective Study of Nicotine from Edible Solanaceae and Risk of Parkinson Disease

 描述（由申请人提供）：帕金森病（PD）是美国第二常见的神经退行性疾病，影响超过100万美国人;由于人口老龄化，这一数字正在增长。大多数患者最终发展为严重残疾，这明显影响了他们及其照顾者的生活质量。因此，迫切需要开发疾病改善或神经保护治疗。在以前的流行病学研究中，吸烟一直被证明与男性和女性的PD风险降低有关。基于这些观察结果，尼古丁被认为是一种潜在的神经保护剂。然而，吸烟和较低的PD风险之间的关联可以通过一个仍然未知的第三个因素来解释，该因素增加了PD的风险，也导致了对吸烟行为的厌恶。在这种情况下，重要的是要检查来自其他来源而不是香烟的尼古丁是否也与PD风险改变相关。由于少量尼古丁可以饱和大脑中的大部分尼古丁受体，因此我们能够检查饮食尼古丁消耗对PD风险的潜在影响。这将为支持或反对尼古丁与PD风险改变之间的潜在因果关系提供强有力的证据，对于开发新型预防/治疗策略也很重要。因此，我们建议进行一项大规模的前瞻性研究，以检查饮食中摄入尼古丁和含尼古丁的茄科植物是否与两个正在进行的美国队列中的PD风险相关，其中包括超过78，000名从未吸烟的男性和女性。在26-32年的随访中，我们记录了921例PD事件，因为饮食数据被收集。我们建议检查1）饮食尼古丁和含尼古丁的茄科植物的更多消费是否与发展PD的风险降低有关，以及2）饮食尼古丁之间的关联是否在没有环境烟草烟雾暴露的人群中更明显。作为次要目的，我们将研究尼古丁饮食摄入量与趾甲尼古丁水平之间的关联，趾甲尼古丁水平是1，217名HPFS/NHS从不吸烟者中尼古丁暴露的长期生物标志物，两种数据均可用。最后，我们将探讨饮食尼古丁和遗传因素之间可能的相互作用（即，CHRNA 5，iNOS 2a和SNCA），这些基因先前已被证明可以改变吸烟与PD的关系。值得注意的是，有超过900例PD病例，这是唯一一项对PD风险因素进行的大型前瞻性研究，其中包括对饮食和其他生活方式因素的重复和详细评估。鉴于烟草中的尼古丁可能具有不良影响，膳食尼古丁的疾病调节潜力具有重要价值。这一结果很容易在临床实践中转化，因为食用的安全性，可接受性和广泛的可用性。 茄科食品。

 DESCRIPTION (provided by applicant): Parkinson disease (PD) is the second most common neurodegenerative disease in the United States and affects over one million Americans; this number is growing due to population aging. Most patients eventually develop severe disability, which markedly affects their quality of life and that of their caregivers. There is thus a compellig need to develop disease modifying or neuroprotective treatments. In previous epidemiologic studies, cigarette smoking has been consistently shown to be associated with a lower risk of PD in men and women. Based on these observations, nicotine has been proposed to be a potential neuro-protective agent. However, the association between smoking and lower PD risk could be explained by a still-unknown third factor that increases the risk of PD and also causes an aversion to smoking behavior. In this context, it is of importance to examine whether nicotine from other sources, rather than cigarettes, is also associated with altered PD risk. Because a small amount of nicotine can saturate a substantial portion of nicotine receptors in the brain, we thus are able to examine the potential effects of dietary nicotine consumption on PD risk. This would provide strong evidence arguing for or against the potential casual relationship between nicotine and altered PD risk and is also important for the development of a novel prevention/treatment strategy. We thus propose to conduct a large-scale prospective study to examine whether dietary intake of nicotine and nicotine-containing solanaceae is associated with PD risk in two ongoing US cohorts including over 78,000 men and women who had never smoked. During 26-32 years of follow-up, we documented 921 incident cases of PD since dietary data were collected. We propose to examine 1) whether greater consumptions of dietary nicotine and nicotine-containing solanaceae are associated with lower risk of developing PD and 2) whether the association between dietary nicotine is more pronounced among those without environmental tobacco smoke exposure. As a secondary aim, we will examine the association between dietary intake of nicotine and toenail nicotine level, a long-term biomarker of nicotine exposure among 1,217 HPFS/NHS never-smokers with both data available. Finally, we will explore possible interactions between dietary nicotine and genetic factors (i.e., CHRNA5, iNOS2a, and SNCA) among never-smokers which have been previously shown to modify the smoking-PD relationship. Of note, with over 900 incident PD case, this is the only large prospective investigation of PD risk factors that includes repeated and detailed assessments of diet and other lifestyle factors. Given nicotine from tobacco may have adverse effects, the disease-modifying potential of dietary nicotine is of great value. This result could easily be translated in clinical practices due to the safety, acceptableness, and wide availability of edible solanaceae foods.